Series of new-3-amino-2-oxazolidones and the preparation thereof



Patented Sept. 15, 1953 SERIES OF NEW 3-A1iflNO-2-OXAZOLIDONES AND THE PREPARATION THEREOF.

Gabriel Gever, Oxford, N. Y., assignor to Eaton Laboratories, Inc., Norwich, N

tionof New York Y., a corpora- No Drawing. Application February 28, 1952, Serial No. 274,067

7 Claims. (01. 260-307) This invention relates to a new series of chemical compounds and the preparation thereof. The V series consists of a number 3-amino-2-oxazolidones. the general formula:

of closely related They are described by wherein R is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl R1 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl R2 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl, and R3 is a member of the group consisting of hydrogen, lower alkyl and hydroxy, (lower) alkyl.

The new compounds of the series are particularly useful as intermediates for the preparation of members of a series of N-(5-nitr0-2-furyD- alkylidene 3 amino-2-oxazolidones, notably, N-(5-nitro-2-furfurylidene)-3-amino 2 oxazolidone, which I have invented and which form R3 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl.

2 'The reactants are heated together and any alcohol formed during the reaction is removed by fractional distillation to encourage the reaction to proceed to completion. An alkaline metal catalyst in small quantity is desirable in the reaction mixture in order that the reaction will take place smoothly. Such a catalyst is sodium methylate.

An alternative method of preparing the various members of the new series or 3-amino-2-oxazolidones is by the catalytic reduction of the corresponding 3-nitro-2 oxazolidone derivative. The nitro compound is prepared by nitration of the selected 2-oxazolidone derivative under known conditions for the preparation of nitro derivatives. Hydrogenation of the nitro compound is carried out at atmospheric pressure and at a temperature within the range of 0 to 5 C. using Adams platinum oxide as a catalyst. In approximately 5 hours nearly the theoretical amount of hydrogen is absorbed, whereupon the catalyst is filtered out.

The 3-nitro-2-oxazolidone may also be reduced electrolytically. In this method, sulfuric acid is employed as the catholyte, lead as the anode, a mercury pool as 30 density of 0.204 amp/cm? is used for 1 hour at duces the desired S-amino-Z-oxazolidone derivative from the the cathode, and a current a temperature of 5 to 10 C. This reduction procorresponding 3-nitro-2-oxazolidone.

Another method of preparing the various members of the new series of 3-amino-2-ox- 'azolidones which I have invented is by the treatment with acid solution of a 2-(2-hydroxyalkyl) semicarbazide hydrochloride.

In this method, the hydroxyalkyl semicarbazide, for example,

"2-(2-hydroxyethyl) semicarbazide, is added portion-wise to a refluxed solution of water and hydrochloric acid. Following the completion of the addition of the hydroxyethyl semicarbazide, the mixture is further refluxed for approximately 30 minutes, at the end of which time the solution is cooled and the reaction is complete.

In order that my invention may be entirely available to those skilledin the art, methods for making a number of thelnew compounds of the series are described briefly:

EXAMPLE I 3-amino-2-omzolidone H,N-N--c=0 o onh cfh of 14.2 g., 69% M. P.. 55-62 0. .By recrystallizar tion from ethanol the meltingpoint. is' raised to- B. To a suspension of 2.3 .g. of 3 -nitro-2- oxazolidone in a mixture of 37.66 cc. of'waterand 12.34 cc. of 4.053 N hydrochloric acid is added 0.07 g. of Adams platinum oxide catalyst. Hydrogenation is then carried out at atmospheric pressure and ata temperature of '0-5" C. After 5 hours, 101% of the theoretical amount of hydrogen is absorbed- The catalyst is removed by filtration, leaving a solution of 3-.amino-2- oxazolidone in 55'% y'ield.

C. 3-nitro-"2-oxazolidone is reduced electrolytically, using 160 cc. of sulfuric acid as the catholyte, a leadanode, a mercury pool cathode and a current density of 0.204 amp/cm. for one hour at a temperature of 5-10 0. At the end of this time the aqueous solution is separated from the mercury. I

D. Amix'tur'e of 1500 cc. of water and 500 cc. of concentratedhydrochloric acid is heated to refluxand 100 g'. of, Z-'(2-hydroxyethyl) semicarbazide hydrochloride added in small portions. The resulting solution is refluxed .ior 30 minutes and then cooled to room temperature.

II 3-amzn'o-5-methyZ-2-oscazolidone A mixture "slowly distilled. When the distillation of ethanol ceases, :after about 1 hour, the residue is cooled and diluted with 20 cc. of isopropanol. The resulting precipitate of 3-amino-5-methyl- 2-oxazolidone is removed by filtration. Recrystallization .from isopropanol gives 14.4 g., 24.8%

about 1 hour, the

I (prepared :by

of product, M. P. 40-42 C. The pure material after several recrystallizations melts at 50.3- 50.5 C 1 Y EXAMPLE In 3-umino-.4,5-dimethyl-Zwmazolidone 'HzNN----C=O 0 e -e 'CHa C'Ha To a solution of 13 g. or sodium in 15 cc. of methanol is added 18.? g. of 3-hydrazino-2-butanol (prepared by the condensation of 2,3- epoxybutane with hydrazine hydrate) and 23.5

g. of diethyl carbonate. The mixture is refluxed for 1 hour, with stirring, ;and then the methanol,

' bonate and :a solution of '4 ethanol, excess diethyl carbonate and unreacted 3-hydrazino-2-butanol removed by vacuum distillation.

3-amino-4-butyl-2-owazolidone H1NNC=O 0 GEHa(CH:)aCH-CH: Aamixture 01195- 5g. of 2-hydrazino-l-hexanol I the reduction of ethyl o-hydrazinocaproate "with lithium aluminum hydride), '10 g. of .diethyl carbonate and a solution of 0.35 g. of sodium in 5 cc. of methanol is refluxed for 2 hours. A small amount of insoluble material is removed by filtration and the filtrate distilled in vacuo. A forerun of methanol, ethanol, excess diethyl' carbonate and unreacted 2-hyd-razino-1- hexanol is first obtained. The product of the reaction, 3-.amino-4 butyl-2-oxazolidone, distills at 135 C../0;7 Lmm.

EXAMPLE V 3-a mino-S-hydroxymethyLZ-oazazolidone HzN-N-C=O H2CH onion Asolution of 43' 'g. of sodium hydroxide in 250 g. of hydrazine hydrate is warmed to 40 C. and then'treated dropwise with g. of glycerol oemonochlorohydrin, over a period of 15 minutes, the temperature rising to 110. The

reaction mixture is then heated on the steam bath for 80 minutes and the water and excess hydrazine removed in vacuo. The residue is diluted with "absolute alcohol 'and the sodium chloride present-removed by filtration. The filtrate is concentratedin vacuo to remove the alcohol. To the residual oil is added cc. of diethyl car- 1 g. of sodium in 25 ccr'of methanol. Ihis mixtureiiszheated and the ethanol formed in :the reaction is slowly distilled over a period of 3%hours.

CH2 CH3 4,4-dimethy'l-i3-nitro-2-oxazolidone (3.96 g.) is reduced electrolytically under .the conditions given in Example I, section C. After the aqueous solution is separated from the mercury, it is neutralized with barium hydroxide, the barium sulfate removed by filtration and the filtrate evaporated in 'vacuo to 'remove the water. The residue is taken up in a small amount of absolute alcohol, the excess barium hydroxide filtered off, and the filtrate distilled. After the removal of the alcohol, the 3-amino-4,4-dimethrepresented by R is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl R1 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl R2 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl, and R3 is a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alleyl. 2. 3-amino-2-oxazolidone represented by the formula:

HzN-N-C=O o o1norn 3. 3 amino methyl represented by the formula:

- 2 oxazolidone 5. 3 amino 4 butyl 2 oxazolidone represented by the formula:

6. 3 amino 5 hydroxymetlryl 2 oxazoliclone represented by the formula:

- oxazolidone 7. The method of preparing a 3 -amino-2- oxazoliolone represented by the formula:

HaN-N o=o I \O o 0 R/ R1 Rg Rs wherein R represents a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl R1 represents a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) represents a member of the group consisting of hydrogen, lower alkyl anclhydroxy (lower) alkyl R3 represents a member of the group consisting of hydrogen, lower alkyl and hydroxy (lower) alkyl which comprises reacting a fi-hydroxyalkylhydrazine represented by the formula:

References Cited in the file of this patent UNITED STATES PATENTS Name Date Homeyer Apr. 23, 1946 OTHER REFERENCES Reeueil Travaux Chimiques des Pays-Bas 21, pp.45- (1902).

Number 

1. A NEW CHEMICAL COMPOUND REPRESENTED BY THE FORMULA: 